Synthesis and Characterization of Block Copolymers of Styrene-maleic Acid with Acrylamide and N,N-dimethylacrylamide

Styrene-maleic acid (SMA) block copolymers with either acrylamide (AM) or N,N-dimethylacrylamide (DMA) have been synthesized via a 3-step process comprising: (1) photopolymerization of styrene and maleic anhydride in solution to yield an alternating styrene maleic anhydride (SMAnh) copolymer, (2) copolymerization of SMAnh with either AM or DMA to yield SMAnh-b-AM and SMAnh-b-DMA block copolymers and (3) hydrolysis of the anhydride groups to yield water-soluble SMA-b-AM and SMA-b-DMA block copolymers as the final products. With a view to their intended application in membrane protein solubilization, molecular weights are controlled to below 10,000 by the synthesis conditions employed in step (1), including using carbon tetrabromide (CBr4) as a chain transfer agent. The CBr4 also plays an important role in step (2). By terminating the SMAnh chain radicals from step (1) with C-Br bonds that are photolytically active, SMAnh chain radicals can be regenerated to act as macroinitiators for the polymerization of AM or DMA in step (2). Finally, following step (3) and due to the pH-dependency of the SMA chain conformation in solution, a pH of 7-8 is found to be optimal for enabling the final products to be precipitated in a solid form that is completely soluble in water

Structural design of contact lens-based drug delivery systems; in vitro and in vivo studies of ocular triggering mechanisms

This study identifies and investigates the potential use of in-eye trigger mechanisms to supplement the widely available information on release of ophthalmic drugs from contact lenses under passive release conditions. Ophthalmic dyes and surrogates have been successfully employed to investigate how these factors can be drawn together to make a successful system. The storage of a drug-containing lens in a pH lower than that of the ocular environment can be used to establish an equilibrium that favours retention of the drug in the lens prior to ocular insertion. Although release under passive conditions does not result in complete dye elution, the use of mechanical agitation techniques which mimic the eyelid blink action in conjunction with ocular tear chemistry promotes further release. In this way differentiation between passive and triggered in vitro release characteristics can be established. Investigation of the role of individual tear proteins revealed significant differences in their ability to alter the equilibrium between matrix-held and eluate-held dye or drug. These individual experiments were then investigated in vivo using ophthalmic dyes. Complete elution was found to be achievable in-eye; this demonstrated the importance of that fraction of the drug retained under passive conditions and the triggering effect of in-eye conditions on the release process. Understanding both the structure-property relationship between drug and material and in-eye trigger mechanisms, using ophthalmic dyes as a surrogate, provides the basis of knowledge necessary to design ocular drug delivery vehicles for in-eye release in a controllable manner

Tetracycline-Loaded Electrospun Poly(L-lactide-co-ε-caprolactone) Membranes for One-Step Periodontal Treatment

In this research, a one-step periodontal membrane, with the required function and properties, has been designed as an alternative method of tissue regenerative treatments. Designed nanoporous prototypes from poly(l-lactide-co-ε-caprolactone) (PLCL, 70:30 mol %) were fabricated by electrospinning, denoted as S-PLCL. They were subsequently loaded with tetracycline (TC) in order to enhance periodontal regeneration and deliver an anti-inflammatory and antibiotic drug. It was found that TC loading did not have any significant effect on the fiber diameter but did increase hydrophilicity. With the increase in TC loading, the water vapor permeability (WVP) of the S-PLCL membrane decreased within the range of 31–56% when compared with neat S-PLCL membranes, while in the solvent-cast film (F-PLCL), no significant change in WVP was observed. Moreover, S-PLCL demonstrated a controllable slow release rate of TC. S-PLCL loaded with 1500 μg/mL of TC showed a release concentration of 30 ppm over a certain time period to promote greater levels of human oral fibroblast and human oral keratinocyte cell proliferation and plaque inhibition. In conclusion, a TC-loaded S-PLCL fibrous membrane has been designed and fabricated to provide the ideal conditions for cell proliferation and antibiotic activity during treatment, outperforming nonfibrous F-PLCL loaded with TC at the same concentration

3D-printed PLA/PEO blend as biodegradable substrate coating with CoCl2 for colorimetric humidity detection

This study aimed to fabricate biodegradable substrate with colorimetric humidity indicator for detective moisture in food packaging. The poor properties of poly(lactic acid) (PLA) were enhanced by melt blending PLA with non-toxic poly(ethylene oxide) PEO at 180 °C. Specifically, three-dimensional (3D) substrates of PLA/PEO blends were fabricated by solvent-cast 3D printing. Furthermore, cobalt chloride (CoCl2) solution was printed onto the substrate with an inkjet printer to serve as a colorimetric humidity sensing indicator. It found that the flexibility and thermal stability of the PLA were improved and the hydrophilicity was increased with an increase in PEO content. Color changes and the sensitivity of this material were confirmed using image analysis and total color difference. The CoCl2 indicator displayed color changes that ranged from blue to pink under ambient conditions (above 60%RH), revealing suitable potential for frozen food packaging material with aim to detect amount of moisture in the packaging

Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa

Ionic and neutral hydrogels for dermal and ophthalmic applications

The first area of study is the use of skin adhesive bioelectrode hydrogels as ground plate electrodes for ophthalmic iontophoresis applications. The work provides a basis of understanding the relative contributions made by ionic monomers (such as sodium s-(acrylamide)-2-methyl propane sulphonate and acrylic acid-bis-(3-sulfopropyl-ester, potassium salt) and neutral monomers (such as acryloymorpholine, N,N-dimethylacrylamide and N-vinyl pyrrolidone) to adhesion, rheology and impedance of bioelectrode gels. The general advantage of neutral monomers, which have been used to successfully replace ionic monomers, is that they enable more effective control of independent anion and cation species (for example potassium chloride and sodium chloride) unlike ionic monomers where polymerisation produces an immobile polyanion thus limiting cation mobility. Secondly, release from a completely neutral hydrogel under the influence of mechanical shaking was studied for the case of crosslinked polyvinyl alcohol (PVA) containing low concentration of linear soluble PVA in a contact lens application. The soluble PVA was observed to be eluting by reptation from the lens matrix due to the mechanical action of the eyelid. This process was studied in an in vitro model, which in this research was used as a basis for developing a lens made with enhanced release polymer. The third area of work is related to the factors that control drug release (in particular non-steroidal anti-inflammatory drugs) from a hydrogel matrix. This links both electrotherapy applications, such as transcutaneous electrical nerve stimulation, in which the passive diffusion from the gel could be used in conjunction with enhanced transmission across the dermal surface with passive diffusion from a contact lens matrix and the development of therapeutic contact lenses.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Ionic and neutral hydrogels for dermal and ophthalmic applications

This thesis is concerned with the use of ionic and neutral hydrogels in dermal and ocular applications with particular reference to controlled release applications. The work consists of three interconnected themes.The first area of study is the use of skin adhesive bioelectrode hydrogels as ground plate electrodes for ophthalmic iontophoresis applications. The work provides a basis of understanding the relative contributions made by ionic monomers (such as sodium s-(acrylamide)-2-methyl propane sulphonate and acrylic acid-bis-(3-sulfopropyl-ester, potassium salt) and neutral monomers (such as acryloymorpholine, N,N-dimethylacrylamide and N-vinyl pyrrolidone) to adhesion, rheology and impedance of bioelectrode gels. The general advantage of neutral monomers, which have been used to successfully replace ionic monomers, is that they enable more effective control of independent anion and cation species (for example potassium chloride and sodium chloride) unlike ionic monomers where polymerisation produces an immobile polyanion thus limiting cation mobility. Secondly, release from a completely neutral hydrogel under the influence of mechanical shaking was studied for the case of crosslinked polyvinyl alcohol (PVA) containing low concentration of linear soluble PVA in a contact lens application. The soluble PVA was observed to be eluting by reptation from the lens matrix due to the mechanical action of the eyelid. This process was studied in an in vitro model, which in this research was used as a basis for developing a lens made with enhanced release polymer. The third area of work is related to the factors that control drug release (in particular non-steroidal anti-inflammatory drugs) from a hydrogel matrix. This links both electrotherapy applications, such as transcutaneous electrical nerve stimulation, in which the passive diffusion from the gel could be used in conjunction with enhanced transmission across the dermal surface with passive diffusion from a contact lens matrix and the development of therapeutic contact lenses

Synthesis and characterization of semi-IPN hydrogels composed of sodium 2-acrylamido-2-methylpropanesulfonate and poly(ε-caprolactone) diol for controlled drug delivery

Semi-interpenetrating polymer network (semi-IPN) hydrogel of sodium 2-acrylamido-2-methylpropane sulfonate (Na-AMPS) and poly(ε-caprolactone) (PCL) diol for drug delivery applications was synthesized via free radical UV-photopolymerization technique using 2-hydroxy-4′-(2-hydroxyethoxy)-2-methylpropiophenone as an initiator and poly(ethylene glycol) diacrylate (PEGDA) as a crosslinker. The hydrogels' chemical structure and internal morphology have been explored using Fourier-transform infrared spectroscopy and scanning electron microscopy. The influence of PCL diol and PEGDA concentrations on the synthesized semi-IPN hydrogel properties was investigated. The semi-IPN hydrogel can increase the elasticity of the hydrogel while simultaneously providing enough water uptake and water retention. Furthermore, the semi-IPN hydrogel was non-cytotoxic to mouse fibroblasts L929 cells. Finally, ciprofloxacin (CIP) was used as a model drug and was efficiently encapsulated into the semi-IPN hydrogels. Drug loading capacity was enhanced with increasing PCL diol and CIP content. It was also observed that the PCL diol and CIP contents had a marked influence on the release profiles. Thus, the rate of release could be designed by changing the Na-AMPS to PCL diol ratio and CIP content. Drug release was found to be both diffusion and swelling-controlled in accordance with the Fickian and non-Fickian transport mechanisms. In the light of the results obtained, their easy formability, their appropriate mechanical and physical properties make P(Na-AMPS)/PCL diol semi-IPN hydrogels are the potential candidates for use as drug carrier and controlled drug release materials in the biomedical field

Formulation, adsorption performance, and mechanical integrity of triamine grafted binder-based mesoporous silica pellets for CO2 capture

This work explored the formation of mesoporous silicas pellets using a range of bentonite and colloidal silica (LUDOX) fractions, aiming to optimise the binder composition that minimises any deteriorating effects on adsorption performance, while providing adequate mechanical integrity. Thermogravimetric analysis, scanning electron microscopy, and dynamic mechanical analysis were used to structurally characterise the pellets. Further, CO 2 adsorption isotherms of synthesised pellets, pre and post triamine grafting, were measured. Bentonite was found to be an effective single binder that forms mechanically strong pellets and retains up to 85% of CO 2 capacity of the base adsorbent. In the presence of LUDOX, pellet hardness was lower, and led to the largest decrease in CO 2 capacity. Formulation with 25% bentonite was found to provide pellets with post triamine functionalisation CO 2 capacity equivalent to powder SBA-15, at an amine efficiency of 0.41 mol CO 2/mol, while minimising pore blockage and maintaining a compressive strength of 1.5 MPa

Enhancement of Poly(vinyl alcohol) Hydrogel Properties by N-Succinyl Chitosan and Mesona chinensis Extract for Use as Wound Dressings

Hydrogels composed of different ratios of poly(vinyl alcohol), N-succinyl chitosan (NSC), and Mesona chinensis extract, for use as a wound dressing, were synthesized via thermal polymerization. Potassium persulfate was chosen as the initiator and glutaraldehyde as the crosslinking agent. NSC was prepared by modification of chitosan with succinic anhydride. It was found that this preparation method gave a high gel fraction percentage. The structures of the prepared hydrogels were characterized by Fourier-transform infrared spectroscopy, and their morphology by scanning electron microscopy (SEM). In addition, water transport properties, mechanical properties and cytotoxicity were also studied. The SEM results show that the hydrogels exhibited porous structures and that pore size and size distribution increased with increasing NSC content. Hydrogel-water interactions and water transport properties were also studied in terms of swelling ratio, equilibrium water retention, and water vapour transmission rate. These showed an increase, from 637 to 1240 %, 17.8 to 21.4 %, and 110 to 121 g h−1 m−2 respectively with an increase in NSC content. These gels exhibit a lower water vapour transmission rate compared to that of second and third degree burns but higher than normal skin. Similarly, NSC improved the mechanical properties, presented in terms of stress and percentage strain, of the hydrogels. The stress, percentage strain, and Young’s modulus were found to increase from 15 to 32 kPa, 197 to 294 %, and 0.078 to 0.133 kPa respectively. The hydrogels can be considered to be non-toxic based on the in vitro cytotoxicity assay results. In conclusion, the results showed that, by varying composition, hydrogel properties can be tuned to the specific requirements of an ideal wound dressing